Colon cancer is a major medical problem in the United States today. It is the second leading cause of death with 47,000 deaths per year reported. The distribution of colon cancer, particularly its infrequency in Japan, its increase among Japanese immigrants to Hawaii, and the high incidence of this disease in North Americans and Northwest Europeans, indicates that an environmental factor is of etiological significance in the development of this disease. Recent studies have demonstrated an association of colon cancer with a high degree of bacterial transformation of the bile acids and sterols in feces. The role played by these metabolites as possible co-carcinogens and how their colonic concentrations might be altered are the objectives of the proposed research. In order to define more precisely the importance of the bacterial transformants, we will study the effect of induced changes in their colonic concentrations on cancer development in rats given carcinogens. In addition, we will investigate an important detoxifying mechanism in man (sulfation) in retarding tumor development. Factors which influence the degree of bacterial transformation in both normal subjects and subjects with a high risk of cancer will be investigated. Methods of altering the colonic concentration of the bacterial metabolites will be sought. Finally, the epithelial cell kinetics of subjects and rats with different colonic concentrations of bacterial metabolites will be investigated. From these studies we hope to be able to identify patients with a high risk of developing cancer and develop means of decreasing this risk.